This study was to scientifically and systematically explore the association between cardiotoxicity and immune checkpoint inhibitors (ICIs) and also to characterize the spectrum of ICI-related cardiac complications. From the first quarter of 2014 to the fourth quarter of 2019, data from the FDA Adverse Event Reporting System database were selected to conduct the disproportionality analysis. Reporting odds ratios and information components were used to evaluate the signal after statistical shrinkage transformation. In total, 7,443,137 cases and 36,326,611 drug-adverse event pairs were collected, among which 9,271 cases were identified to be related to ICI-induced cardiotoxicities. The number of male patients was much higher than that of females (5,579 vs. 3,031) and males presented a slightly higher reporting frequency than females in general, which was statistically significant (ROR = 1.04, 95%CI: 0.99–1.09, p < 0.001). Simultaneously, the proportion of serious or life-threatening outcomes in males was significantly higher than in females (ROR = 1.05, 95%CI: 0.96–1.15, p < 0.001). Importantly, ICIs were associated with over-reporting frequencies of cardiotoxicities in general (ROR025 = 1.06, IC025 = 0.08). PD-1 and PD-L1 were found to be related to cardiac adverse events, corresponding to ROR025 = 1.06, IC025 = 0.08, and ROR025 = 1.06, IC025 = 0.08, respectively, while anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) was significantly associated with some specific adverse events rather than common adverse events. The spectrum of cardiotoxicities induced by ICIs mostly differed among individual agents, but also demonstrated some common features. Dyspnea (N = 2,527, 21.25%), myocarditis (N = 614, 5.16%), atrial fibrillation (N = 576, 4.84%), cardiac failure (N = 476, 4.00%), and pericardial effusion (N = 423, 3.56%) were the top five cardiac adverse events reported in the database. Among them, myocarditis was the only one caused by all ICIs with strong signal value and high risk, warranting further attention. Overall, this investigation mainly showed the profile of cardiotoxicities caused by ICIs, which varied between different ICI therapies, but also shared some similarities in specific symptoms such as myocarditis. Therefore, it is vital and urgent to recognize and manage ICI-related cardiotoxicities, known to frequently occur in clinical practice, at the earliest point.

Background: Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs-induced renal toxicities and the potential effects of chemotherapy. Methods:We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR 025 and IC 025 are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR 025 exceeding one or IC 025 higher than zero, then a signal was considered statistically significant.Results: A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs-associated renal AEs. Renal AEs were more frequently reported in anti-PD-1/PD-L1 versus anti-CTLA-4 monotherapy group (ROR: 1.75, 95% CI: 1.52-2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10-1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17-1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs-associated renal AEs, and also observed with the top two highest level of fatality outcome rates. Conclusions:A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome

Disproportionality analysis by information components (ICs) were used to evaluate the potential association between adverse events (AEs) and alpelisib.Results: A total of 33 327 reports were extracted, 5695 of them were chosen with alpelisib as the suspected drug. After combining the same ID, 687 cases remained. The 45-64-years group had the most cases (n = 203, 29.55%). There were 129 Preferred Terms with significant signals. Hyperglycaemia (IC025 = 6.74), breast cancer metastatic (IC025 = 5.85) and metastases to liver (IC025 = 4.70) were the AEs with the strongest signal. AEs with the most cases were hyperglycaemia (n = 595), rash (n = 535) and diarrhoea (n = 475). Conclusion:We established a comprehensive list of AEs potentially associated with alpelisib. AEs with the most significant signals were hyperglycaemia, breast cancer metastatic, metastases to liver. The AEs with the most cases were hyperglycaemia, rash, diarrhoea, blood glucose increase and nausea.

No abstract

Background: Although ibrutinib has been widely used to treat haematological malignancies, many studies have reported associated cardiovascular events. These studies were primarily animal experiments and clinical trials. For more rational clinical drug use, a study based on post-marketing data is necessary. Aim: Based on post-marketing data, we investigated the clinical features, time to onset, and outcomes of potential cardiovascular toxicities of ibrutinib. Methods: This disproportionality study utilised data from the 2014–2021 United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used two disproportionality methods information component (IC) and reporting odds ratio (ROR)) to detect the potential cardiovascular toxicities of ibrutinib. Positive signals were defined as IC025 > 0 and ROR025 > 1. Results: A total of 10 cardiovascular events showed positive signals: supraventricular tachyarrhythmias, haemorrhagic central nervous system vascular conditions, ventricular tachyarrhythmias, cardiac failure, ischaemic central nervous system vascular conditions, cardiomyopathy, conduction defects, myocardial infarction, myocardial infarction disorders of sinus node function, and torsade de pointes/QT prolongation. Cardiomyopathy and supraventricular tachyarrhythmias were the two most common signals. Disorders of sinus node function were observed for the first time, which may be a new adverse effect of ibrutinib. Conclusions: This pharmacovigilance study systematically explored the adverse cardiovascular events of ibrutinib and provided new safety signals based on past safety information. Attention should be paid to some high-risk signals.